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Longevity Briefs: How Does Fasting Suppress The Immune System?

Posted on 12 September 2022

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Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: Fasting and other forms of dietary restriction (DR), which simply refers to a sharp reduction in calories without malnutrition, is generally considered to be a very healthy practice. One of the few potential downsides of DR is that it seems to temporarily reduce the production of new T and B cells. This might actually benefit the immune system in the long term, with some studies suggesting that people who fast are protected against autoimmune diseases and infection in the long run. However, studies disagree about whether people are more or less vulnerable to infection during DR. Scientists also don’t know how exactly DR suppresses the production of new immune cells.

A simplified view of blood cell production. The highlighted lymphoid lineage give rise to specialised T and B cells, and is suppressed during dietary restriction. This lineage also becomes less active with older age.
Principles and Comparative Aspects of Adaptive Immunity

What did the researchers do: There’s a well known link between diet, the bacteria in our guts, and the immune system. In this study, researchers wanted to investigate whether the gut bacteria had anything to do with DR’s effects on immune cells. They took mice that had their food restricted by 30% for 4 weeks. Some of these mice were then fed broad-spectrum antibiotics in order to destroy their gut bacteria, while others were given a control treatment. Researchers then studied how the immune cell populations in these mice were affected.

Key takeaway(s) from this research: The researchers found that mice undergoing dietary restriction had reduced numbers of immune cells, including common lymphoid progenitor cells in the bone marrow, which are the cells capable of developing into specialised immune cells like T and B cells. However, in the mice treated with antibiotics, the effects of DR on the immune system were significantly reduced: antibiotic-treated mice generally had fewer immune cells than mice that were fed normally, but more than the untreated DR mice.

Further investigations helped explain these differences: during DR, mice experienced a change in the composition of their gut microbiota. This lead to an increase in the production of butyrate, a fatty acid produced by gut bacteria when they ferment carbohydrates that we are unable to digest. When researchers gave supplementary butyrate to normally-fed mice, the effects on their immune cells were similar to those of DR. This suggests that signals from gut bacteria are at least partly responsible for immune suppression during DR, explaining why mice treated with antibiotics didn’t experience as large a reduction in immune cells.

We don’t yet know if these findings will apply to humans or what practical applications they could have, but studies continue to suggest that manipulating the gut microbiome is a promising way to promote healthy ageing. We also know that the deterioration of the immune system is an important factor when it comes to ageing. Understanding the details of how these systems interact will be very useful in the future.

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    Gut microbiota mediates the inhibition of lymphopoiesis in dietary-restricted mice by suppressing glycolysis:

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